Single-nucleotide polymorphism array and fluorescence in situ hybridization analysis to decode the cytogenetic profile of atypical partial hydatidiform moles diagnosed by short tandem repeat polymorphism analysis.

Accurate diagnosis of partial hydatidiform moles (PHMs) is crucial for improving outcomes of gestational trophoblastic neoplasia. The use of short tandem repeat (STR) polymorphism analysis to distinguish between PHM and hydropic abortuses is instrumental; however, its diagnostic power has not been comprehensively assessed. Herein, we evaluated the diagnostic efficacy of STR in differentiating between PHM and hydropic abortus, thus providing an opportunity for early measurement of human chorionic gonadotropin for PHMs. We reviewed charts of STR polymorphism analysis performed on fresh villous specimens and patient blood samples using a commercial kit for 16 loci. The genetic classification of 79 PHMs was confirmed. STR was reliable in differentiating PHMs when at least 15 loci were available. Typically, PHMs are characterized by their triploidy, including two paternal and one maternal haploid contribution. In our sample, seven PHMs lacked the three-allelic loci, requiring fluorescence in situ hybridization (FISH) analysis to investigate imbalanced biparental conceptus and single-nucleotide polymorphism array analysis to reveal cytogenetic details. Of these PHMs, two, three, and one were identified as androgenetic/biparental mosaics (diploids), monospermic diandric monogynic triploids, and a typical dispermic diandric monogynic triploid, respectively. The remaining case was monospermic origin, but its ploidy details could not be available. Therefore, STR differentiated PHM from a biparental diploid abortus in most cases. However, PHM diagnosis may be compromised when STR is used as the sole method for cases displaying distinct cytogenetic patterns lacking the three-allelic loci, including androgenetic/biparental mosaicism. Therefore, FISH should be considered to confirm the diagnosis.

Placental mesenchymal disease masquerading as molar pregnancy with a favourable maternal and fetal outcome.

Placental mesenchymal dysplasia (PMD) is an exceptionally rare placental anomaly characterised by placentomegaly and grape-like vesicles resembling partial mole on ultrasonography, yet it can coexist with a viable fetus. We present the case of a primigravida who presented at 22 weeks gestation with a suspected partial mole but with a normally growing fetus. The differential diagnoses considered included placental mesenchymal disease, partial mole and twin pregnancy with molar pregnancy. With normal beta HCG levels and prenatal invasive testing reports, a probable diagnosis of PMD was made, and after thorough counselling, the decision was made to continue the pregnancy. The pregnancy progressed until 37 weeks, culminating in the uneventful delivery of a 2.4 kg healthy male infant. Histopathology confirmed PMD. Early recognition and management of PMD pose significant challenges, given its rarity. Prenatal identification of PMD during both early and late gestation could avert unnecessary termination of pregnancy.

Partial Molar Ectopic Pregnancy: A diagnostic challenge.

Here, we present a rare case of a primigravida who presented to us with symptoms and signs suggestive of an ectopic gestation, which turned out to be a partial mole in histopathological examination. Since it is a very rare occurrence, we would like to publish the case details in this case report.

Short tandem repeats genotyping of gestational choriocarcinoma - our experiences.

OBJECTIVE: This short communication demonstrates how short tandem repeat genotyping can identify the origin of gestational choriocarcinoma. MATERIALS AND METHODS: The origin of gestational choriocarcinoma in our three cases was determined using the short tandem repeats genotyping technique, which involved quantitative fluorescent PCR and fragmentation analysis. RESULTS: In Case 1 despite no medical history of molar pregnancy, DNA analysis indicated that the choriocarcinoma originated from a homozygous complete hydatidiform mole. We conclude, that the patient's complete abortion 10 years prior to the choriocarcinoma diagnosis was an undiagnosed complete hydatidiform mole. In Case 2 and Case 3 the clinically presumed origin of choriocarcinoma was confirmed. CONCLUSION: Determining the origin of choriocarcinoma is essential for clinical application, as it affects the FIGO scoring system for gestational trophoblastic neoplasia, which determines the patient's prognosis and treatment approach.

Practical guidelines of the EOTTD for pathological and genetic diagnosis of hydatidiform moles.

Hydatidiform moles are rare and thus most pathologists and geneticists have little experience with their diagnosis. It is important to promptly and correctly identify hydatidiform moles given that they are premalignant disorders associated with a risk of persistent gestational trophoblastic disease and gestational trophoblastic neoplasia. Improvement in diagnosis can be achieved with uniformization of diagnostic criteria and establishment of algorithms. To this aim, the Pathology and Genetics Working Party of the European Organisation for Treatment of Trophoblastic Diseases has developed guidelines that describe the pathological criteria and ancillary techniques that can be used in the differential diagnosis of hydatidiform moles. These guidelines are based on the best available evidence in the literature, professional experience and consensus of the experts' group involved in its development.

Twin pregnancy with incomplete hydatidiform mole and coexistent normal live fetus: A case report and review of the literature.

RATIONALE: A pregnancy with incomplete mole is very rare case. Hydatidiform mole (HM) with live fetus is associated with a risk of a wide variety to maternal and fetal complications. The incidence of a normal live fetus and an incomplete mole such as the case we describe is extremely rare. PATIENT CONCERN: We report a case of multiparous 34-year-old at Culiacan Mexico woman with incomplete mole coexisting with normal fetus, pregnant 35.3 weeks who presented anemia grade II. DIAGNOSIS: The initial diagnosis of the mole was by ultrasound. INTERVENTIONS: KERR-type cesarean section and bilateral tubal occlusion. The newborn was morphologically normal, and she did not require intervention or treatment. OUTCOMES: The newborn was feminine, morphologically normal, weighing 2380 g and 47 cm, APGAR score 8 to 9, delivered prematurely, and there was a large placental plate. The blood loss on surgery was estimated at 1000 mL. Histopathology report of an incomplete hydatidiform mole, negative for malignancy. Histopathology diagnostic was confirmed by immunohistochemistry staining for p57KIP2. LESSONS: Although the incidence of this pregnancy is very rare, early recognition, diagnosis and divulge of the cases of medical community is very important for patient care.

Double Trisomy 16 and 22 Clinically Mimic Partial Hydatidiform Mole in a Case of Subsequent Pregnancy Loss.

A case of double trisomy 16 and 22 in the second pregnancy loss is presented. DNA analyses (short tandem repeats genotyping) of miscarriage specimen was indicated because of ultrasound suspicion of partial hydatidiform mole. After the partial hydatidiform mole exclusion, further DNA analyses focused on the most common aneuploidies causing pregnancy loss, detected double trisomy 16 and 22 in the product of conception. The couple was referred to clinical genetic consultation and normal parental karyotypes were proved. For further explanatory purposes, archived material from the first pregnancy loss was analyzed and trisomy of chromosome 18 was detected. By comparison of allelic profiles of the mother, father, and both losses, the maternal origin of all aneuploidies was proven what can be attributed to frequent meiosis errors, probably due to advanced maternal age (44 years at the first loss and 45 years at the second loss). In conclusion, aneuploidies can mimic partial hydatidiform mole. Genetic analysis is helpful on the one hand to rule out partial hydatidiform mole and on the other hand to identify aneuploidies and in this way to determine the cause of miscarriage.

Recurrent choriocarcinoma complicated with leprosy during chemotherapy: A case report and literature review.

RATIONALE: The global prevalence of leprosy has decreased substantially, and cases of leprosy infection are extremely rare in China. In this report, we present a case of recurrent choriocarcinoma complicated by leprosy infection during chemotherapy. PATIENT CONCERNS: A 24-year-old Chinese woman (gravida 3, para 2) presented to a local hospital with vaginal bleeding. Her medical history included a previous diagnosis of hydatidiform mole. DIAGNOSES, INTERVENTIONS AND OUTCOMES: The patient was diagnosed with choriocarcinoma and received chemotherapy in 6 cycles. Shortly after the initial treatment was completed, the disease recurred twice with resistance to multiple chemotherapeutic agents. In her second recurrence of choriocarcinoma, she was diagnosed with leprosy with many cutaneous nodules throughout her entire body. The patient was administered chemical treatment for leprosy with the multidrug therapy regimen after being diagnosed. To prevent exacerbating the infection, no immunotherapy was utilized to treat cancer, and the infection was well-controlled at the conclusion of anticancer therapy. LESSONS: Because of immunological reduction, cancer patients are susceptible to a variety of infections. For patients with cancer, prevention and early detection of rare infectious diseases should receive special attention. Immunotherapy must be used with caution when treating patients with cancer and infections.

Hydatidiform mole.

Hydatidiform mole is the most common form of gestational trophoblastic disease. It is an abnormally formed placental tissue with characteristic changes in karyotype, arising in fertilization disorders. The presence of abundant paternal genetic information plays a key role in the pathogenesis of complete and partial hydatidiform moles. These lesions are characterized by a relatively wide spectrum of morphological changes that may not be fully expressed, especially in the early stages of pregnancy. In addition, some changes can be observed in non-molar gravidities, which, unlike hydatidiform moles, lack any risk of malignant transformation. Although conventional histological examination still plays a key role in the diagnosis, it should be supplemented by other methods that reliably differentiate individual lesions. Accurate diagnosis of molar gravidities is important not only for determining the correct therapeutic approach, but the obtained data may also contribute to further research of these pathological entities.

Molecular diagnosis of complete and partial hydatidiform moles.

Complete and partial hydatidiform moles are abnormal products of conception that can be identified by clinical, ultrasonographic, morphologic, histologic, and genetic methods. The diagnosis is usually confirmed only by histological examination. However, accurate diagnosis based on morphological criteria is difficult and some studies have shown that misclassifications are common, even when analysed by highly experienced pathologists. Misdiagnosis may mean that women are either not included in adequate ß-hCG follow-up with the risk that the hydatidiform mole progresses to choriocarcinoma or, conversely, are included in follow-up unnecessarily. A reliable complementary method to pathological interpretation may be genetic analysis of the conceptus to eliminate the diagnostic dilemma by distinguishing non-molar spontaneous abortions from hydatidiform moles and defining the type of hydatidiform mole. The aim of our short paper is to introduce the routine molecular analysis used in our laboratory to a wider range of clinical pathologists.

Unpacking the importance of histopathology in ectopic pregnancy: Vital for follow up.

The incidence of ectopic molar pregnancy is very rare with an incidence estimated to be 1.5 per 1,000,000 pregnancies. The pre-operative diagnosis is rare and needs careful histopathological examination of salpingectomy specimen. A case of a 34-year-old female is discussed who presented in shock with clinical and radiological diagnosis of ruptured ectopic pregnancy and histopathology report revealed partial mole in ectopic specimen.

Metastatic choriocarcinoma of the kidney in the absence of existing primary uterine tumor: A rare presentation.

Gestational choriocarcinomas are malignant neoplasms generally arising in the uterus in women of childbearing age. These are aggressive tumors with a high incidence of metastasis to vascular organs such as the lung, liver, and brain. Renal metastasis is extremely rare with low incidence rate and very few cases have been reported in literature. Hereby, we report a rare case of metastatic choriocarcinoma to the kidney in a 29-year-old female 10 years after resection of a hydatidiform mole. The histopathological diagnosis was made on a nephrectomy specimen. Pelvic and abdominal scan did not show any abnormal radiological findings. She was started on first-line chemotherapy and showed a complete response. In conclusion, gestational or primary nongestational choriocarcinomas should always be considered as a differential diagnosis in young females of reproductive age group presenting with flank abdominal pain, unexplained hematuria, and atypical renal tumor histology.

Diagnostic Utility of TSSC3 and RB1 Immunohistochemistry in Hydatidiform Mole.

The general notion of complete hydatidiform moles is that most of them consist entirely of paternal DNA; hence, they do not express p57, a paternally imprinted gene. This forms the basis for the diagnosis of hydatidiform moles. There are about 38 paternally imprinted genes. The aim of this study is to determine whether other paternally imprinted genes could also assist in the diagnostic approach of hydatidiform moles. This study comprised of 29 complete moles, 15 partial moles and 17 non-molar abortuses. Immunohistochemical study using the antibodies of paternal-imprinted (RB1, TSSC3 and DOG1) and maternal-imprinted (DNMT1 and GATA3) genes were performed. The antibodies' immunoreactivity was evaluated on various placental cell types, namely cytotrophoblasts, syncytiotrophoblasts, villous stromal cells, extravillous intermediate trophoblasts and decidual cells. TSSC3 and RB1 expression were observed in all cases of partial moles and non-molar abortuses. In contrast, their expression in complete moles was identified in 31% (TSSC3) and 10.3% (RB1), respectively (p < 0.0001). DOG1 was consistently negative in all cell types in all cases. The expressions of maternally imprinted genes were seen in all cases, except for one case of complete mole where GATA3 was negative. Both TSSC3 and RB1 could serve as a useful adjunct to p57 for the discrimination of complete moles from partial moles and non-molar abortuses, especially in laboratories that lack comprehensive molecular service and in cases where p57 staining is equivocal.

Tubal ectopic twin pregnancy of complete hydatidiform mole and coexisting embryo: A rare case report.

RATIONALE: Ectopic twin gestation involving a complete hydatidiform mole (CHM) and coexisting embryo is an exceedingly rare occurrence. PATIENT CONCERNS: In this report, we present the case of a 22-year-old female (gravida2, para 1) who was in her 8th week of gestation and presented with abdominal pain. Due to the detection of active bleeding and a ruptured right fallopian tube, the patient underwent a salpingectomy on the right side. DIAGNOSIS: The patient was diagnosed with an ectopic twin gestation involving a CHM and coexisting embryo. INTERVENTIONS: The patient was treated with right-side salpingectomy. OUTCOMES: The operation was successful and her recuperation was satisfactory. LESSONS: In the management of ectopic pregnancy involving CHM, it is crucial to enhance the accuracy of preoperative diagnosis. Additionally, histopathological examination of the salpingectomy specimen and conceptus is definitely essential for accurate diagnosis and appropriate follow-up management of tubal pregnancies.

Immunohistochemical expression of BCL-2 in hydatidiform moles: a tissue microarray study.

Background: Hydatidiform moles (HM) are members of gestational trophoblastic diseases (GTD) and, in some cases, might progress to gestational trophoblastic neoplasia (GTN). HMs are either partial (PHM) or complete (CHM). Some HMs are challenging in arriving at a precise histopathological diagnosis. This study aims to investigate the expression of BCL-2 by immunohistochemistry (IHC) in HMs as well as in normal trophoblastic tissues "products of conception (POC) and placentas" using Tissue MicroArray (TMA) technique. Methods: TMAs were constructed using the archival material of 237 HMs (95 PHM and 142 CHM) and 202 control normal trophoblastic tissues; POC and unremarkable placentas. Sections were immunohistochemically stained using antibodies against BCL-2. The staining was assessed semi-quantatively (intensity and percentage of the positive cells) in different cellular components (trophoblasts and stromal cells). Results: BCL-2 showed cytoplasmic expression in more than 95% of trophoblasts of PHM, CHM and controls. The staining showed a significant reduction of the intensity from controls (73.7%), PHMs (76.3%) to CHM (26.9%). There was a statistically significant difference between PHM and CHM in the intensity (p-value 0.0005) and the overall scores (p-value 0.0005), but not the percentage score (p-value > 0.05). No significant difference was observed in the positivity of the villous stromal cells between the different groups. All cellular components were visible using the TMA model of two spots/case (3 mm diameter, each) in more than 90% of cases. Conclusions: Decreased BCL-2 expression in CHM compared to PHM and normal trophoblasts indicates increased apoptosis and uncontrolled trophoblastic proliferation. Construction of TMA in duplicates using cores of 3 mm diameter can overcome tissue heterogeneity of complex lesions.

Misdiagnosis of placental mesenchymal dysplasia as pregnancy with hydatidiform mole: A case report and literature review.

RATIONALE: Placental mesenchymal dysplasia (PMD) is a rare placental disease frequently associated with severe maternal and/or fetal complications. Its sonographic appearance is very similar to that of a hydatidiform mole. Hence, PMD is easily misdiagnosed as a hydatidiform mole. In this study, we reported the clinical features of PMD and analyzed its relationship to other severe maternal and/or fetal complications. PATIENT CONCERNS: A 28-year-old female, gravida 2, para 1, was referred to our maternal and child health hospital at 15 weeks + 2 days due to an ultrasonic diagnosis of partial hydatidiform mole. Analysis of chromosome karyotype + mononucleotide-based gene microarray by amniocentesis at the 19th week of gestation showed that fetal amniocentesis chromosome 46, XN, high-resolution chromosome microarray analysis of Affymetrix CytoScan 750K Array revealed a 210 kb fragment deletion in chromosome 2p16.3 containing NRXN1, an OMIM gene, the deleted fragment was derived from a mother with a normal phenotype. The pregnant woman delivered a healthy baby girl at 36 weeks + 5 days. DIAGNOSES: Based on the clinical characteristics, imaging, and genetic test findings, the postoperative diagnosis was PMD. INTERVENTION: Because of "Scar uterus" and "Pregnancy with hydatidiform mole," a 2490 g female infant was delivered by cesarean section at 36 weeks + 5 days of gestation with an Apgar score of 9/9. OUTCOMES: The maternal human chorionic gonadotropin level decreased to the normal range after 10 days of delivery, and the infant was not found abnormal after 3 months of follow-up. LESSONS: From our cases and 19 other cases obtained from the PMD literature review are associated with unique clinical, laboratory, and imaging features compared with a hydatidiform mole, such as stained glass sign, normal serum levels of serum human chorionic gonadotropin, elevated alpha-fetoprotein levels and female fetus.